B. Background The co-morbid rates of nicotine dependence in patients with major depression are estimated to be 50-60% [1-3]. Smokers with a history of major depression disorders have great difficulty quitting smoking compared to smokers without a history of major depression [2, 4]. Furthermore, smokers with a history of depression appear to be at substantial risk for the emergence of depressive symptom exacerbation, typically within one month after smoking cessation [2, 5-7], though this phenomenon has been recently questioned [8]. Recent estimates are that nearly 45% of all cigarettes consumed in the USA are by individuals with mental illness [10].